Arachidonic acid release by H2O2 mediated proliferation of mouse embryonic stem cells: Involvement of Ca2+/PKC and MAPKs‐induced EGFR transactivation |
| |
Authors: | Sang Hun Lee Sun Im Na Jung Sun Heo Min Hee Kim Yun Hee Kim Min Young Lee Seong Hong Kim Yun Jung Lee Ho Jae Han |
| |
Affiliation: | Department of Veterinary Physiology, Biotherapy Human Resources Center (BK 21), College of Veterinary Medicine, Chonnam National University, Gwangju 500‐757, South Korea |
| |
Abstract: | Reactive oxygen species (ROS) generated by a variety of endogenous factors and roles in embryonic stem (ES) cells has yet to be identified. Thus, we examined role of arachidonic acid (AA) in H2O2‐indued proliferation of mouse ES cells and its related signaling molecules. AA release was maximally increased in response to 10?4 M H2O2 for 1 h. In addition, H2O2 increased intracellular Ca2+ concentration ([Ca2+]i) and the phosphorylation of protein kinase C (PKC), p44/42, p38 mitogen‐activated protein kinase (MAPK), and JNK/SAPK. Moreover, H2O2 induced an increase in the phosphorylation of epidermal growth factor receptor (EGFR), which was blocked by the inhibition of p44/42 or p38 MAPKs. The inhibition of each signal molecule with specific inhibitors blocked H2O2‐induced cytosolic phospholipase A2 (cPLA2) activation and AA release. H2O2 increased NF‐κB phosphorylation to induce an increase in the levels of cyclooxygenase (COX)‐2 proteins. Subsequently, H2O2 stimulated PGE2 synthesis, which was reduced by the inhibition of NF‐κB activation. Moreover, each H2O2 or PGE2 increased DNA synthesis and the number of cells. However, H2O2‐induced increase in DNA synthesis was inhibited by the suppression of cPLA2 pathway. In conclusion, H2O2 increased AA release and PGE2 production by the upregulation of cPLA2 and COX‐2 via Ca2+/PKC/MAPKs and EGFR transactivation, subsequently proliferation of mouse ES cells. J. Cell. Biochem. 106: 787–797, 2009. © 2009 Wiley‐Liss, Inc. |
| |
Keywords: | H2O2 ROS arachidonic acid PGE2 EGFR mouse ES cell proliferation |
|
|